PROJECT SUMMARY The research project planned in this diversity research supplement for Dr. Wilnelly Martinez-Ortiz is constructed based on her research expertise in chemistry, computational structural biology and molecular/cell biology and desire to further her postdoctoral training in chemical biology and small molecule cancer drug discovery for epigenetic proteins. At the same time, this research project that is being developed and refined by Dr. Martinez-Ortiz under the mentorship from Dr. Ming-Ming Zhou is expected to facilitate the Zhou lab?s ongoing efforts in deciphering the fundamental molecular mechanisms that underlie major transcription regulator proteins as they pertain to the epigenetic regulation of gene transcription in biology and human cancers, as described in the parent grant (1R01CA239165-01, PI: MMZ). Specifically, Dr. Wilnelly Martinez-Ortiz will employ the structure-based rational design strategy to develop novel small molecule compounds, which will be used as powerful research tools to study the functional role of BET transcription proteins as key components of the important transcriptional activation complex for gene transcription in chromatin. We expect that this planned research project will help prepare Dr. Wilnelly Martinez-Ortiz to become fully an independent investigator in academic research, who will be capable of identifying most challenging problems in biomedical research, and conceiving and developing scientific approaches to address such problems in human biology and disease.